Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance.

Abstract

BACKGROUND:

Angiopoietin-2 is a proinflammatory mediator of endothelial injury in animal models, and increased plasma angiopoietin-2 levels are associated with poor outcomes in patients with sepsis-associated acute lung injury. Whether angiopoietin-2 levels are modified by treatment strategies in patients with acute lung injury is unknown.

OBJECTIVES:

To determine whether plasma angiopoietin-2 levels are associated with clinical outcomes and affected by fluid management strategy in a broad cohort of patients with acute lung injury.

DESIGN, SETTING, AND PARTICIPANTS:

Plasma levels of angiopoietin-2 and von Willebrand factor (a traditional marker of endothelial injury) were measured in 931 subjects with acute lung injury enrolled in a randomized trial of fluid liberal vs. fluid conservative management.

MEASUREMENTS AND MAIN RESULTS:

The presence of infection (sepsis or pneumonia) as the primary acute lung injury risk factor significantly modified the relationship between baseline angiopoietin-2 levels and mortality (p = .01 for interaction). In noninfection-related acute lung injury, higher baseline angiopoietin-2 levels were strongly associated with increased mortality (odds ratio, 2.43 per 1-log increase in angiopoietin-2; 95% confidence interval, 1.57-3.75; p < .001). In infection-related acute lung injury, baseline angiopoietin-2 levels were similarly elevated in survivors and nonsurvivors; however, patients whose plasma angiopoietin-2 levels increased from day 0 to day 3 had more than double the odds of death compared with patients whose angiopoietin-2 levels declined over the same period of time (odds ratio, 2.29; 95% confidence interval, 1.54-3.43; p < .001). Fluid-conservative therapy led to a 15% greater decline in angiopoietin-2 levels from day 0 to day 3 (95% confidence interval, 4.6-24.8%; p = .006) compared with fluid-liberal therapy in patients with infection-related acute lung injury. In contrast, plasma levels of von Willebrand factor were significantly associated with mortality in both infection-related and noninfection-related acute lung injury and were not affected by fluid therapy.

CONCLUSIONS:

Unlike von Willebrand factor, plasma angiopoietin-2 has differential prognostic value for mortality depending on the presence or absence of infection as an acute lung injury risk factor. Fluid conservative therapy preferentially lowers plasma angiopoietin-2 levels over time and thus may be beneficial in part by decreasing endothelial inflammation.

• Authors: Carolyn S Calfee, Diana Gallagher, Jason Abbott, B Taylor Thompson, Michael A Matthay, NHLBI ARDS Network
• Journal: Critical care medicine (Crit Care Med) Vol. 40 Issue 6 Pg. 1731-7 (Jun 2012) ISSN: 1530-0293 [Electronic] United States
• PMID: 22610178 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-2
• Biomarkers
• von Willebrand Factor

Topics

• Acute Lung Injury (blood, mortality, therapy)
• Adult
• Aged
• Angiopoietin-2 (blood)
• Biomarkers (blood)
• Female
• Fluid Therapy (methods)
• Humans
• Male
• Middle Aged
• Prognosis
• Risk Factors
• Sepsis (blood)
• Treatment Outcome
• von Willebrand Factor (analysis)